This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The Light and Electron Microscopic (LM/EM) Imaging Core Facility provides image acquisition and analysis services on a fee-per-use basis. The facility contains a broad range of instruments that allow visualization of fixed tissue, in vitro cell and tissue preparations and in vivo imaging. Broadly, instrumentation can be divided into standard fluorescence-based capabilities such as upright microscopes with digital camera image capture and confocal microscopy that we term linear optical microscopy (LOM) to contrast with non-linear optical microscopy (NLOM) methods that are based on scanning with fast-pulsed lasers, such as multiphoton microscopy. The facility is staffed with two doctorate-trained managers to facilitate expert consultation for experimental design, training on use of equipment, and efficient access to equipment for data collection. The NLOM system is designed as a technology development core through collaboration with a faculty member and trainees in physics to devise new approaches to biomedical imaging. This facility is unique within the state of West Virginia, and the NLOM capabilities are available in very few centers nationwide. Support to further build and sustain NLOM is the focus of our request in this application. The LM/EM Core is directed by a faculty member, Dr. Robert Wysolmerski, who has substantial experience with both LM and EM imaging modalities and who ran an EM core prior to joining WVU. The co-director, Dr. Feruz Ganikhanov, has extensive experience in laser physics and is tasked to develop new imaging applications for NLOM in consultation or collaboration with biomedical scientists. He oversees a laboratory manager who also has doctoral training in laser physics and who assists investigators during data collection and analysis. Because we request support primarily for these NLOM capabilities, we devote much of this section to their description. Newly constructed laboratory space in the Erma Byrd Biomedical Research Building has been allocated for the LM/EM Imaging Core. The third floor of that building houses the NLOM and one confocal microscope;the bulk of the remaining equipment is housed in an integrated facility on the second floor.